OPDM5_ABCD3
- Gene
- ABCD3
- Disease
- OPDM5
- Inheritance
- AD
- Classification
- Moderate
- Total Score
- 10
- Publications Reviewed
- 1
- Publication Span
- Last Updated
- 04/29/2026
- Curator(s)
- Laurel Hiatt, Macayla Weiner, Harriet Dashnow, Elbay Aliyev
Description
A heterozygous CCG repeat expansion in the 5′-UTR/untranslated first exon of ABCD3 was reported as the cause of autosomal dominant oculopharyngodistal myopathy type 5 (OPDM5) in families of European ancestry. PMID:39068203 described 35 affected individuals from eight unrelated families, with detailed clinical data for 24 individuals; targeted ONT long-read sequencing showed monoallelic pure CCG expansions of 118–694 repeats in 19 affected individuals. Genetic support includes linkage in AUS1/AUS2 (maximum LOD 2.98), RP-PCR/optical genome mapping confirmation, segregation in UK2, and a shared ancestral haplotype encompassing ABCD3. Functional data showed increased ABCD3 transcript in OPDM skeletal muscle and patient fibroblasts/muscle, with rare p62-positive intranuclear inclusions in patient skin/fibroblast samples. To date, this locus–disease relationship is supported by one publication.
Genetic evidence
Total: 8.5
| Singular Evidence | Probands | PMID:39068203 | 6 | PMID:39068203 reported 35 affected individuals from eight unrelated OPDM families of European ancestry, with detailed clinical findings for 24 individuals; ABCD3 5′-UTR CCG expansions were identified across families using srWGS/EHdn, RP-PCR, optical genome mapping, and/or targeted ONT long-read sequencing. |
| Collective Evidence | Allele | PMID:39068203 | 1 | Targeted ONT long-read sequencing showed heterozygous pure ABCD3 5′-UTR CCG expansions of 118–694 repeats in 19 affected individuals, while unaffected relatives had two 7-repeat alleles; larger expansions correlated with earlier onset in affected males (n=6, p=0.0063), and female expansions were larger and more variable than male expansions (p=0.0295). |
| Collective Evidence | Segregation | PMID:39068203 | 1.5 | Combined linkage analysis in AUS1 and AUS2 produced a maximum multipoint LOD score of 2.98 across a 24 Mb region containing ABCD3; the expansion segregated in UK2 (affected sister positive, unaffected mother negative), and affected individuals shared a 560 kb ancestral haplotype encompassing ABCD3. |
Experimental evidence
Total: 1.5
| Function | Regulatory impact | PMID:39068203 | 0.5 | RNA-seq and qPCR showed increased ABCD3 transcript in OPDM skeletal muscle compared with neuromuscular disease and healthy controls; HCR RNA-FISH showed increased cytoplasmic and intranuclear ABCD3 sense transcript signal, including nuclear foci-like clusters, in patient fibroblasts and muscle. |
| Functional Alteration | Patient cells | PMID:39068203 | 1 | Patient-derived skin and fibroblast samples from ABCD3 expansion carriers showed rare p62-positive intranuclear inclusions, including in nuclei of skin exocrine glands, keratinocytes, and fibroblasts, and ultra-rare inclusions (<0.1%) in primary skin fibroblasts from AUS3-IV:3; these were absent or less prominent in controls. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.